Formaldehyde → HCID 14457551, compound

HRID 1853295Notes

Reaction equation

HRID 1853295 reaction equation
[CH:1]1[CH:6]=[CH:5][C:4]([CH2:7][N:8]2[CH:12]=[N:11][C:10]([CH2:13][C@H](N)C(O)=O)=[CH:9]2)=[CH:3][CH:2]=1.[CH2:19]=[O:20].S(Cl)(Cl)=O.[OH2:25]>>[CH3:19][O:20][C:9]([CH:10]1[NH:11][CH2:13][C:10]2[N:11]=[CH:12][N:8]([CH2:7][C:4]3[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=3)[C:9]=2[CH2:13]1)=[O:25]

Participants

5

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 24386Thionyl ChlorideHCID 193138Poly(1-benzylhistidine)

Product 1

HCID 14457551HCID 14457551, compoundYield 71%

Conditions

Temperature
0 °C

Procedure

A solution of H-His-(Bzl)-OH (2.0 g, 8.16 mmol) and formaldehyde (37% in water, 0.92 ml, 12.24 mmol) in water (16 ml) was heated to reflux for 4 hours and concentrated to dryness. The residue was dissolved in methanol (4.6 ml) cooled to 0° C. and treated with thionyl chloride (0.6 ml, 8.12 mmol). The reaction mixture was reflux for 2.5 hours and concentrated. The solid was dissolved in dichloromethane, washed with a saturated solution of sodium hydrogenocarbonate, brine, dried over sodium sulfate and concentrated to dryness to yield 1-Benzyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid methyl ester (1.58 g, 71%). The ester was dissolved in tetrahydrofuran (26 ml), cooled to 0° C. and treated with 2,3-Dichloro-5,6-dicyanobenzoquinone (2.9 g, 12.81 mmol) in tetrahydrofuran (26 ml) and the reaction mixture was reflux for 4 hours. The solvent was removed and the black residue was dissolved in dichloromethane and treated with a 1M aqueous solution of sodium hydroxide. The aqueous solution was extracted several times with dichloromethane. The combined organic extracts were washed with brine, dried over sodium sulfate, concentrated and purified by flash chromatography over silica gel (gradient ethyl acetate/methanol: 0-10%) to yield 1-Benzyl-1H-imidazo[4,5-c]pyridin-6-carboxylic acid methyl ester (525 mg, 34%) as a beige solid.

Workup

  1. temperatureto reflux for 4 hours
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was dissolved in methanol (4.6 ml)
  4. temperatureThe reaction mixture was reflux for 2.5 hours
  5. concentrationconcentrated
  6. dissolutionThe solid was dissolved in dichloromethane
  7. washwashed with a saturated solution of sodium hydrogenocarbonate, brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-9f68472973ea40e8acfe4a8c3dd9c4d0
Source dataset
uspto-grants-2015_02
Patent number
US08962627B2

Reaction notes

Loading…